Contemporary Risk Stratification and Treatment of Chronic Myelomonocytic Leukemia

Tremblay, Douglas; Rippel, Noa; Feld, Jonathan; Jamal, Siraj M. El; Mascarenhas, John

doi:10.1002/onco.13769

Cited by 10 publications

(4 citation statements)

References 136 publications

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“…The overall prognosis of CMML is generally poor, with a median OS time of 17 months ( Guru Murthy et al, 2017 ). Prognosis is stratified according to the CMML-specific Prognostic Scoring System (CPSS) ( Tremblay et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients

Zhang,

Ge,

Pan

et al. 2024

Front. Pharmacol.

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Introduction:Current clinical research has reported the effectiveness and safety of venetoclax in combination with hypomethylating agents (VEN-HMA) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Thus, this study aimed to examine the effectiveness and safety of VEN-HMA therapy in patients with MDS and CMML and compared its short-term and long-term therapeutic effects with HMA monotherapy.Method:We analyzed data from our center, comprising 19 patients with MDS and CMML who received VEN-HMA therapy, compared to 32 patients treated with HMA monotherapy.Results:The overall response rate (ORR) in the VEN-HMA group was 73.7%, compared to 59.4% in the HMA group. The survival analysis revealed that the median overall survival (mOS) time in the VEN-HMA group was 16 months, with a median progression-free survival (mPFS) time of 9 months, both of which were longer than those observed in the HMA group (p < 0.05). Key adverse events (AEs) included grade 3–4 neutropenia (89.5% in VEN-HMA group vs. 87.5% in HMA group), grade 3–4 thrombocytopenia (73.7% vs. 71.9%), and anemia (73.7% vs. 90.6%). Infection of grade 3 or higher occurred in 63.2% of patients in the VEN-HMA group and 65.6% of patients in the HMA group.Discussion:Our study has confirmed the effectiveness and safety of the combined treatment of HMAs and venetoclax, which offers significant advantages to patients due to the relatively high and rapid response rates.

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Section: Introductionmentioning

confidence: 99%

“…Patients with high-risk CMML presenting obvious symptoms should be monitored and given cytotoxic therapy, HMAs, or allo-HSCT. Notably, HMAs are the sole agents approved by the U.S. Food and Drug Administration (FDA) for CMML treatment ( Tremblay et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients

Zhang,

Ge,

Pan

et al. 2024

Front. Pharmacol.

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“…(1,2) Numerous pretreatment prognostic models are well established so far by bone marrow (BM) blasts, abnormal karyotypes, and genetic mutations, which closely associated with clinical prognosis of patients with newly diagnosed CMML and developing adapted treatment strategy. (3,4) Response criterias proposed by International Working Group (IWG) in 2015 according to morphologic analysis also provides much disease speci c prognostic information and re ects chemotherapy sensitivity of leukemia. (5) However, they are not ideal for capturing responses associated with the myeloproliferative features of the disease, such as increased leukocyte and/or monocyte counts and splenomegaly.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Implication of Early Minimal Residual Disease Evaluation in Patients with Chronic Myelomonocytic Leukemia

Wang

Chen

et al. 2022

Preprint

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Background: This article is performed to assess the significance of minimal residual disease (MRD) after one course of therapy in patients with chronic myelomonocytic leukemia (CMML). Methods: From January 2010 to January 2022, a total of 158 patients who were newly diagnosed with CMML were enrolled, in which 58/158 (37%) patients were conducted by multiparameter flow cytometry (FCM) assessed MRD analysis after on cycle treatment and were included in this study. MRD was detected by six- to eight- colour FCM. Result: After one course of therapy, twenty-one (36%) patients achieved MRD<0.01% (MRD1-) and thirty-seven (64%) were MRD>0.01% (MRD1+). The patients in the MRD1+ group had lower platelet counts, higher 𝛽2-microglobulin, ferritin and BM1 myeloblasts (bone marrow myeloblasts after one cycle of therapy) than that of the MRD1- group (P=0.005, P=0.023, P=0.026 and P=0.007, respectively). Furthermore, a greater propotion of patients had JCK2 and SETBP1 mutation in MRD1- patients than in MRD1+ group (both P=0.037). At a median follow up time of 25.8 months (95%CI, 15.01-36.59), those patients who achieved MRD<0.01% after one course of therapy fared better prognosis in terms of both OS (overall survival, 54.9 months vs. 17.5 months; P<0.001) and PFS (progression-free survival, 52.3 months vs 11.9 months; P=0.006) than those of MRD>0.01%, and 2-year OS rate (90% vs. 30%; P<0.001) and 2-year PFS rate (70% vs. 7%; P=0.004) were also higher. MRD1 status could determine the likelihood of progression after hematopoietic stem cell transplantation (HSCT), the 2-year PFS rate (100% vs. 24%, P=0.04) was higher in MRD1+ group than MRD1- group at the post-HSCT assessment. In addition, MRD1 status were independent prognostic factor of both PFS (HR, 3.326 [95%CI, 1.340-8.259]; P=0.01) and OS (HR, 4.614 [95%CI, 1.266-16.812]; P=0.02). Conclusion: MRD is highly predictive of prognosis, and it may help identify patients at increased risk for progression to further improve the management of patients with CMML. Large-scaled investigations are warranted to validate our conclusions and its potential in clinical practice.

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“…Because of all the positive effects of HU therapies, it is nominated as an "essential medicine" by the World Health Organization [2]. Moreover, hydroxyurea is a first-line cytoreduction agent in high-risk patients with a myeloproliferative neoplasm [3].…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro

Kapor

Vukotić

Subotički

et al. 2021

JPM

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Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal stem/stromal cell (BMMSC) functions has not elucidated yet. Our results indicate that HU inhibits the growth of human BMMSC alongside senescence-like changes in both morphology and replicative potential, provokes cell cycle arrest at the S phase without affecting cellular viability and induces the expression of senescence-associated β-galactosidase and p16INK4. Moreover, HU-induced senescent BMMSC, although they did not change MSC markers expression, exhibited reduced capacity osteogenic and adipogenic differentiation. Conversely, HU treatment increased immunoregulatory functions of BMMSC compared with untreated cells and determined by T-cell proliferation. Interestingly, HU did not influence the capacity of BMMSC to induce monocytic myeloid-derived suppressor cells. Thus, these results suggest that HU improves the BMMSC functions on the T-cell inhibition and preserves their interaction with myeloid cell compartment. Mechanistically, BMMSC under HU treatment displayed a downregulation of mTOR and p38 MAPK signaling that may explain the reduced cell differentiation and increased immunomodulation activities. Together, the results obtained in this investigation suggest that HU by inducing senescence-like phenotype of BMMSC influences their cellular differentiation and immunoregulatory functions.

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Contemporary Risk Stratification and Treatment of Chronic Myelomonocytic Leukemia

Cited by 10 publications

References 136 publications

A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients

A real-world experience of venetoclax combined with hypomethylating agents vs. monotherapy hypomethylating agents in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia patients

Prognostic Implication of Early Minimal Residual Disease Evaluation in Patients with Chronic Myelomonocytic Leukemia

Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro

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